RT Journal Article SR Electronic T1 Class I DISARM provides anti-phage and anti-conjugation activity by unmethylated DNA recognition JF bioRxiv FD Cold Spring Harbor Laboratory SP 2021.12.28.474362 DO 10.1101/2021.12.28.474362 A1 Cristian Aparicio-Maldonado A1 Gal Ofir A1 Andrea Salini A1 Rotem Sorek A1 Franklin L. Nobrega A1 Stan J.J. Brouns YR 2021 UL http://biorxiv.org/content/early/2021/12/28/2021.12.28.474362.abstract AB Bacteriophages impose a strong evolutionary pressure on microbes for the development of mechanisms of survival. Multiple new mechanisms of innate defense have been described recently, with the molecular mechanism of most of them remaining uncharacterized. Here, we show that a Class 1 DISARM (defense island system associated with restriction-modification) system from Serratia sp. provides broad protection from double-stranded DNA phages, and drives a population of single-stranded phages to extinction. We identify that protection is not abolished by deletion of individual DISARM genes and that the absence of methylase genes drmMI and drmMII does not result in autoimmunity. In addition to antiphage activity we also observe that DISARM limits conjugation, and this activity is linked to the number of methylase cognate sites in the plasmid. Overall, we show that Class 1 DISARM provides robust anti-phage and anti-plasmid protection mediated primarily by drmA and drmB, which provide resistance to invading nucleic acids using a mechanism enhanced by the recognition of unmethylated cognate sites of the two methylases drmMI and drmMII.Competing Interest StatementThe authors have declared no competing interest.